Nanotechnology has been of great interest in academic and industrial research for the past several decades. After many years of intense research efforts, nanoscaled technology is beginning to yield commercial applications in the automotive, electronics, consumer, and healthcare industries (1–8). The pharmaceutical and cosmetics industries have used the unique properties of nanosized molecules for diagnosing and monitoring diseases, delivering drugs, repairing damaged tissues, and mitigating disease states (9–18). Classes of nanosized systems used in the pharmaceutical industry are liposomes, nanocrystals, micelles, colloidal particles, quantum dots, and dendrimers (19–24), to name a few. Dendrimers, in particular, have attracted attention for their drug-delivery applications because of the ease of their synthesis, the ability to achieve well-defined shapes and sizes (monodispersity), and their chemical diversity compared with synthetic polymers (25). Because of dendrimers' interior void space and surface functional groups, they are well-suited for use as carrier molecules in drug delivery (26).

Dendrimers are a unique class of synthetic macromolecules that can be distinguished from classical linear polymers by their highly branched, monodispersed, circular, and symmetrical architecture (see Figure 1). The term dendrimer was derived from its 'tree-like' structural architecture. A typical dendrimer structure consists of a core molecule (C), multiple layers or generations of branched molecules (G), and surface molecules (S). The first synthetic procedure for producing these structures was published in 1978 by Vögtle, who used a procedure described as a "cascade" synthesis (27). It was Tomalia's group, working at Dow Chemical (Midland, MI), which extensively studied the first dendritic structures of polyamidoamine (PAMAM) (28). It was discovered that these polymeric macromolecules synthesized by the "divergent" synthesis technique provided rich functionality on the outer surface (see Figure 1).

In 1989, Fréchet introduced a more convenient and superior synthetic procedure for producing greater purity dendrimers described as the "convergent" technique (29). This revolutionized the field of dendrimer science. Irrespective of the synthetic routes, each route has its own advantages and disadvantages.

A dendrimer: a polymeric macromolecule

Dendrimers are synthesized by a repetitive step-growth polymerization process. For example, Starburst (Starpharma, Melbourne, Australia) (PAMAM) dendrimers with a diaminobutane core are synthesized with alternating reaction with acrylic acid methyl ester and ethylenediamine (28). This repetitive sequence of reaction steps theoretically allows the macromolecular dimensions of dendrimers to be controlled precisely. This resulting impressive structure has much more monodisperse molecules than is possible for classical linear polymers, which tend to be polydispersed.

When a dendrimer reaches generation greater than about four during the step-wise synthetic process (depending on its chemistry), it undergoes a significant conformational change and assumes a densely packed globular shape (30). This change in dendrimer conformation imparts solution and bulk properties that differ from regular linear or branched polymers. Another important characteristic that distinguishes dendrimers from more conventional polymers is their intrinsic viscosity (31). It is well known that the intrinsic viscosity of linear polymers is proportional to its molecular weight and concentration. In contrast, dendrimers exhibit a bell-shaped viscosity curve, where viscosity increases at lower generation numbers, reaching a maximum, which corresponds to a change in the conformation and beyond which the intrinsic viscosity decreases at a higher molecular weight. This feature is very useful in formulation science, as these high-molecular-weight, higher-generation dendrimers do not tend to be highly viscous and are therefore easy to handle and formulate. Another important attraction of using dendrimers for delivery systems comes from their property of being highly soluble in a large number of organic solvents (32).

The surface functional groups impart significant physical properties to the dendrimer in the solid and solution states. By proper choice of surface functional group chemistry and building units, unique physical and chemical properties can be created (29, 32). This approach has been exploited by pharmaceutical scientists in designing carrier systems of molecules, for linking to individual molecules (dendrimer-molecule conjugates) and for engineering specific interactions with biological systems such as receptors (33–34).

Several excellent review articles describing applications of dendrimers in nanomedicines have been published (35–39). Dendrimers such as PAMAM have been widely studied, and researchers have found diverse applications for them in biomedical and biological sciences (40–44). In particular, dendrimers have been used as carriers for drug delivery by various routes of administration, including parenteral, oral, topical, transdermal, and ocular. Although widely researched for more than two decades, only one clinical study is underway using dendrimers as microbicides (43). Studies performed for ocular or topical application have not shown dendrimers to be irritating or toxic to the biological tissue. This review will focus on the use of dendrimers for topical routes of administration, including applications in cosmetics or personal care products, as well as for drug delivery to or through skin or to the eye.